DEVELOPMENT OF NOVEL REACTIVE SULFUR SPECIES DONORS

Abstract

Reactive sulfur species are important cell signaling molecules. Among them, hydrogen sulfide (H2S), hydrogen polysulfides (H2Sn, n>1), persulfides (RSSH), and S-nitroso hydrogen sulfide (HSNO) are believed to be mediators of many physiological and/or pathological processes. However, the mechanism (s) of action for these reactive sulfur species is far from clear. Further, these molecules are unstable and difficult to handle. Their instability is the major roadblock hindering their biological understanding. Having the access to their reliable and controllable precursors (or donors) is the prerequisite for the study of these reactive sulfur species. To this end, we have developed new controllable reactive sulfur species donors, such as phosphonothioate-based H2S donors, cyclic acyl disulfides and O-silyl-based donors. These molecules were stable in aqueous solutions. However, in the presence of certain activation conditions, time-dependent reactive sulfur species release was observed. In addition, protective effects of these donors in living systems were also observed. These findings suggest that these molecules are potent reactive sulfur species donors and they have potential therapeutic benefits.